Antimicrobial resin compositions

ABSTRACT

Methods for making antimicrobial resins and for forming coatings comprising antimicrobial resins on substrate surfaces are disclosed. The methods involve providing a mixture comprising about 15 weight % to about 80 weight % of a hydrophilic acrylic oligomer, about 10 weight % to about 80 weight % of a multifunctional acrylic monomer, about 5 weight % to about 40 weight % of an adhesion-promoting acrylic or vinyl monomer, and about 0.1 weight % to about 15 weight % of a metal salt; and exposing the mixture to a radiation source to cure at least a portion of the mixture, thereby forming an antimicrobial resin.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a divisional application of U.S. patent applicationSer. No. 12/145,548, filed Jun. 25, 2008, the entire disclosure of whichis incorporated herein by reference.

BACKGROUND

1. Field of the Disclosure

The disclosure relates generally to antimicrobial resin compositions andmethods for making such resins. More particularly, the disclosure isdirected to methods of making antimicrobial resin compositionscomprising antimicrobial metal salts and methods for forming such resinson substrates, such as medical devices.

2. Brief Description of Related Technology

Even brief exposure to surfaces contaminated with microbes can introducebacterial, viral, fungal, or other undesirable infections to humans andother animals. Of particular concern is preventing or reducing microbialinfection associated with the use of invasive medical devices such ascatheters, intravenous fluid administration systems, and similar medicaldevices which require prolonged patient contact and thus presentsignificant infection risks. Contamination may result from the patients'own flora or from one or more healthcare workers' hands during insertionand/or manipulation of the device, or from both the patient andhealthcare worker. Medical devices coated with antimicrobial materialscan reduce the transfer of such microbes to patients, thereby improvingthe safety and efficacy of these devices. Such antimicrobial coatingsoften include silver metal or silver salts, or other metals withdemonstrable antimicrobial activity such as copper, gold, zinc, cerium,platinum, palladium, or tin.

Silver and salts thereof are commonly used in antimicrobial coatingsbecause of their demonstrated broad spectrum antimicrobial activityagainst various bacteria, viruses, yeast, fungi, and protozoa. It istheorized that the observed antimicrobial activity is primarily due tothe ability of silver ions to tightly bind nucleophilic functionalgroups containing sulfur, oxygen or nitrogen. Many nucleophilicfunctional groups such as thiols, carboxylates, phosphates, alcohols,amines, imidazoles, and indoles are prevalent in biomolecules. Uponbinding of ionized silver to these various nucleophilic functionalgroups, it is believed that widespread disruption and inactivation ofmicrobial biomolecules (and thus antimicrobial activity) occurs.

Silver and salts thereof have therefore been used as antimicrobialagents in a wide variety of applications; for example, they have beenincorporated in the absorbent materials of wound care products such asdressings, gels, and bandages, and also in compositions for providingantimicrobial coatings on medical devices. Polymeric componentsfrequently are added to such silver- or silver salt-containingcompositions in order to facilitate manufacturing and/or deposition. Onedisadvantage of such antimicrobial compositions, however, is theircharacteristic poor adhesion to substrate surfaces. Strong adhesion tosurfaces is frequently desirable to maintain continued release of theantimicrobial agent over a period of time and to avoid loss of theantimicrobial coating by routine contact with a patient or healthcareworker. Many polymer-containing metal or metal salt compositions alsoexhibit unsatisfactory antimicrobial efficacy profiles. Various factorscan contribute to undesirable efficacy profiles, such as poorlydispersed or settled particles of the metal or metal salt, deformationof the coating during curing, or decomposition of the metal or metalsalt during subsequent sterilization treatments. Poor dispersion of themetal or metal salt in the composition, for example, can result inheterogeneous release of the metal or metal salt, while a well-dispersedmetal or metal salt generally elutes from the composition according tomore homogeneous spatial and/or temporal release profiles. Anotherdisadvantage of many polymer-containing metal or metal salt compositionsis the heterogeneous crosslinked structure that can result, for example,from long polymer cure times and/or imprecise control of the polymercuring conditions. Long polymer cure times and/or imprecisely controlledpolymer curing conditions, for example, can disadvantageously contributeto the formation of poorly dispersed or settled metals or metal salts,and thus can produce compositions having heterogeneous elution profiles.

A disadvantage of antimicrobial compositions comprising metals insteadof metal salts is their characteristic color/opaqueness, which preventsa healthcare provider from being able to see through the medical devicesubstrate. Silver coatings, for example, are generally brown in color.Thus, when silver coatings are applied to transparent surfaces, thecoated surfaces typically have a brown color and significantlydiminished transparency. In contrast to coatings comprising metallicsilver, many coatings comprising silver salts are transparent ortranslucent, and/or lack a colored appearance. Thus, when silver saltcoatings are applied to transparent surfaces, the coated surfacestypically have little color and are highly transparent.

SUMMARY

The present disclosure is directed to methods for forming antimicrobialresins. The methods include providing a mixture comprising a hydrophilicacrylic oligomer, a multifunctional acrylic monomer, anadhesion-promoting acrylic or vinyl monomer, and an antimicrobial metalsalt; and exposing the mixture to a radiation source to cure at least aportion of the mixture, thereby forming an antimicrobial resin. Themethods further include forming medical devices or medical componentscomprising the antimicrobial resin. In accordance with the presentmethods, the antimicrobial resin can be applied to a substrate surfaceto form a coating on the substrate surface. Alternatively, a coatingcomprising an antimicrobial resin can be formed by providing the mixtureon a substrate surface before exposing the mixture to the radiationsource.

The substrate surfaces can comprise plastics, glasses, metals, ceramics,elastomers, or mixtures or laminates thereof. The substrate surfaces cancomprise surfaces of medical devices or medical device components.Preferred examples of substrate surfaces include polycarbonate medicaldevices. The substrate surface also can comprise surfaces of medicalfluid containers or medical fluid flow systems. Preferred examples ofmedical fluid flow systems include I.V. sets and components thereof,such as, for example, luer access devices.

The antimicrobial metal salt can comprise various metals or mixtures ofmetals. Preferred metal salts include salts of silver, copper, gold,zinc, cerium, platinum, palladium, and tin.

The radiation source can be an ultraviolet (UV) light source, anelectron beam source, a gamma radiation source, an X-ray source, an ionbeam source, a microwave source, a heat source, or other radiationsources.

The hydrophilic acrylic oligomer includes acrylic oligomers and mixturesof acrylic oligomers having one or more acrylate, methacrylate,acrylamide, or methacrylamide functional groups. The hydrophilic acrylicoligomer also includes acrylic oligomers having combinations of theforegoing functional groups.

The multifunctional acrylic monomer includes acrylate esters,methacrylate esters, acrylamides, methacrylamides, and mixtures of theforegoing having more than one acrylate, methacrylate, acrylamide, ormethacrylamide functional groups. The multifunctional acrylic monomeralso includes acrylic monomers having combinations of the foregoingfunctional groups.

The adhesion-promoting acrylic or vinyl monomer includes acrylateesters, methacrylate esters, acrylamides, methacrylamides, and mixturesof the foregoing having one or more acrylate, methacrylate, acrylamide,or methacrylamide functional groups. The adhesion-promoting acrylic orvinyl monomer also includes acrylic monomers having combinations of theforegoing functional groups and monomers having vinyl groups.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a graph showing the release of silver ions over time fromsubstrate surfaces carrying an antimicrobial resin prepared inaccordance with the methods of the disclosure (B-1, B-2, B-3), comparedto substrate surfaces carrying antimicrobial resins not prepared inaccordance with the methods of the disclosure (A-1, A-2, A-3, C-1, C-2,C-3, D-1, D-2, D-3).

FIG. 2 is a graph showing the total amount of silver released from thesamples of FIG. 1 after 96 hours.

FIG. 3 is a graph showing the growth over time in colony forming units(cfu) per mL of S. aureus on a polycarbonate substrate surface carryinga coating comprising a cured antimicrobial resin prepared in accordancewith the methods of the disclosure (Sample B), compared to (i) substratesurfaces carrying coatings comprising antimicrobial resins not preparedin accordance with the methods of the disclosure (Sample A, Sample C,and Sample D) and (ii) an uncoated control substrate surface.

DETAILED DESCRIPTION

The present disclosure is directed to methods for forming antimicrobialresins. The methods involve providing a mixture comprising about 15weight % to about 80 weight % of a hydrophilic acrylic oligomer, about10 weight % to about 80 weight % of a multifunctional acrylic monomer,about 5 weight % to about 40 weight % of an adhesion-promoting acrylicor vinyl monomer, and about 0.1 weight % to about 15 weight % of anantimicrobial metal salt; and exposing the mixture to a radiation sourceto cure at least a portion of the mixture, thereby forming anantimicrobial resin. The methods further include forming medical devicesor medical components comprising the antimicrobial resin. In accordancewith the present methods, the antimicrobial resin can be applied to asubstrate surface to form a coating on the substrate surface. In someembodiments, the multifunctional acrylic monomer and the adhesionpromoting acrylic or vinyl monomer can be the same compound.

The present disclosure also is directed to methods for forming a coatingcomprising an antimicrobial resin. The methods involve providing amixture comprising about 15 weight % to about 80 weight % of ahydrophilic acrylic oligomer, about 10 weight % to about 80 weight % ofa multifunctional acrylic monomer, about 5 weight % to about 40 weight %of an adhesion-promoting acrylic or vinyl monomer, and about 0.1 weight% to about 15 weight % of an antimicrobial metal salt; providing themixture on a substrate surface before exposing the mixture to aradiation source; and exposing the mixture to the radiation source tocure at least a portion of the mixture, thereby forming a coatingcomprising an antimicrobial resin.

As previously discussed, many polymer-containing metal or metal saltcompositions adhere poorly to substrate surfaces and/or exhibitunsatisfactory antimicrobial efficacy profiles. Forming antimicrobialresins according to the methods disclosed herein can advantageouslyimprove the dispersion of the metal salt in the resin composition,prevent settling of the metal salt during the curing process, preventdeformation (e.g., shrinking) of the resin during the curing process,and/or produce more homogeneously crosslinked resins. Accordingly,antimicrobial resins prepared according the methods disclosed herein candisplay improved efficacy profiles. Furthermore, coatings comprising theantimicrobial resin can display increased adhesion to substratesurfaces. Accordingly, the disclosed methods can provide efficientmethods for obtaining medical devices comprising a strongly adherentand/or more efficacious antimicrobial coating and, in general, moreefficacious antimicrobial resins.

As described above, many metal-containing compositions aredisadvantageously opaque or colored. Irradiation of compositionscontaining metal salts can reduce the metal salts, thereby producingcompositions comprising metals that can give the composition an opaqueor colored appearance. Surprisingly, and contrary to the expectations ofone of ordinary skill in the art, antimicrobial resins and coatingsthereof prepared by radiation curing in accordance with the presentdisclosure can advantageously be substantially transparent/translucent(upon visual inspection), i.e., generally lacking a colored appearance,despite including ionic metal that one of ordinary skill would expect tobe reduced by the radiation used in the curing process, thereby formingthe corresponding metal which generally causes the compositions tobecome colored. Additionally, radiation curing of the antimicrobialresins of the present disclosure can beneficially obviate the need fordownstream sterilization processing because the resin can be sterilizedby radiation during the curing process.

The substrate surfaces of the present disclosure can comprise variousmaterials including, for example, glasses, metals, plastics, ceramics,and elastomers, as well as mixtures and/or laminates thereof. Suitableexamples of plastics include, but are not limited to, acrylonitrilebutadiene styrenes, polyacrylonitriles, polyamides, polycarbonates,polyesters, polyetheretherketones, polyetherimides, polyethylenes suchas high density polyethylenes and low density polyethylenes,polyethylene terephthalates, polylactic acids, polymethylmethyacrylates, polypropylenes, polystyrenes, polyurethanes, poly(vinylchlorides), polyvinylidene chlorides, polyethers, polysulfones,silicones, and blends and copolymers thereof. Suitable elastomersinclude, but are not limited to, natural rubbers, and synthetic rubbers,such as styrene butadiene rubbers, ethylene propylene diene monomerrubbers (EPDM), polychloroprene rubbers (CR), acrylonitrile butadienerubbers (NBR), chlorosuphonated polyethylene rubbers (CSM), polyisoprenerubbers, isobutylene-isoprene copolymeric rubbers, chlorinatedisobutylene-isoprene copolymeric rubbers, brominatedisobutylene-isoprene copolymeric rubbers, and blends and copolymersthereof.

In one preferred embodiment of the present disclosure, the antimicrobialresin is formed on (or applied to) a surface of a medical device ormedical device component. Medical devices and medical device componentswhich can benefit from the methods according to the disclosure, include,but are not limited to, instruments, apparatuses, implements, machines,contrivances, implants, and components and accessories thereof, intendedfor use in the diagnosis, cure, mitigation, treatment, or prevention ofdisease or other condition in humans or other animals, or intended toaffect the structure or any function of the body of humans or otheranimals. Such medical devices are described, for example, in theofficial National Formulary, the United States Pharmacopoeia, and anysupplements thereto. Representative medical devices include, but are notlimited to: catheters, such as venous catheters, urinary catheters,Foley catheters, and pain management catheters; dialysis sets; dialysisconnectors; stents; abdominal plugs; feeding tubes; indwelling devices;cotton gauzes; wound dressings; contact lenses; lens cases; bandages;sutures; hernia meshes; mesh-based wound coverings; surgical tools;medical monitoring equipment including, but not limited to the touchscreen displays often used in conjunction with such equipment; medicalpumps; pump housings; gaskets such as silicone O-rings; needles;syringes; surgical sutures; filtration devices; drug reconstitutiondevices; implants, metal screws, and metal plates. Additional exemplarymedical devices include, but are not limited to, medical fluidcontainers, medical fluid flow systems, infusion pumps, and medicaldevices such as stethoscopes which regularly come into contact with apatient. One example of a medical fluid flow system is an intravenousfluid administration set, also known as an LV. set, used for theintravenous administration of fluids to a patient. A typical I.V. setuses plastic tubing to connect a phlebotomized subject to one or moremedical fluid sources, such as intravenous solutions or medicamentcontainers. I.V. sets optionally include one or more access devicesproviding access to the fluid flow path to allow fluid to be added to orwithdrawn from the IV tubing. Access devices advantageously eliminatethe need to repeatedly phlebotomize the subject and allow for immediateadministration of medication or other fluids to the subject, as is wellknown. Access devices can be designed for use with connecting apparatusemploying standard luers, and such devices are commonly referred to as“luer access devices,” “luer-activated devices,” or “LADs.” LADs can bemodified with one or more features such as antiseptic indicatingdevices. Various LADs are illustrated in U.S. Pat. Nos. 5,242,432,5,360,413, 5,730,418, 5,782,816, 6,039,302, 6,669,681, and 6,682,509,and U.S. Patent Application Publication Nos. 2003/0141477, 2003/0208165,2008/0021381, and 2008/0021392, the disclosures of which are herebyincorporated by reference in their entireties.

I.V. sets can incorporate additional optional components including, forexample, septa, stoppers, stopcocks, connectors, protective connectorcaps, connector closures, adaptors, clamps, extension sets, filters, andthe like. Thus, suitable medical devices and medical device componentswhich may be processed in accordance with the methods of the presentdisclosure include, but are not limited to: I.V. tubing, I.V. fluidbags, I.V. set access devices, septa, stopcocks, I.V. set connectors,I.V. set connector caps, I.V. set connector closures, I.V. set adaptors,clamps, I.V. filters, catheters, needles, stethoscopes, and cannulae.Representative access devices include, but are not limited to: lueraccess devices including, but not limited to, needleless luer accessdevices.

The surface of the medical device or medical device component can befully or partially coated with the antimicrobial resin. The coating canbe formed on (or applied to) an exterior surface of the device (i.e., asurface which is intended to come into contact with a patient orhealthcare provider), an interior surface of the device (i.e. a surfacewhich is not intended to come into contact with a patient or healthcareprovider, but which can come into contact with the patient's blood orother fluids), or both. Suitable medical devices and medical devicecomponents are illustrated in U.S. Pat. Nos. 4,412,834, 4,417,890,4,440,207, 4,457,749, 4,485,064, 4,592,920, 4,603,152, 4,738,668,5,630,804, 5,928,174, 5,948,385, 6,355,858, 6,592,814, 6,605,751,6,780,332, 6,800,278, 6,849,214, 6,878,757, 6,897,349, 6,921,390, and6,984,392, and U.S. Patent Application Publication No. 2007/0085036, thedisclosures of which are hereby incorporated by reference in theirentireties.

The resins of the present disclosure comprise metal salts havingantimicrobial properties. Suitable metal salts for use in the resinsinclude, but are not limited to, salts of silver, copper, gold, zinc,cerium, platinum, palladium, and tin. Antimicrobial resins comprising acombination of two or more of the foregoing metals can also be used.

Hydrophilic Acrylic Oligomers

Antimicrobial resin compositions in accordance with the presentdisclosure are prepared from a mixture comprising about 15 weight % toabout 80 weight % of a hydrophilic acrylic oligomer. Suitable rangesinclude, but are not limited to, about 25 weight % to about 60 weight %,and/or about 35 weight % to about 50 weight %. The mixture can comprise,for example, about 15 weight % to about 25 weight %, about 25 weight %to about 35 weight %, about 35 weight % to about 45 weight %, about 45weight % to about 55 weight %, about 55 weight % to about 65 weight %,and/or about 65 weight % to about 80 weight % of the acrylic oligomer.Mixtures including more than one acrylic oligomer also can be used.

In accordance with the present disclosure, the hydrophilic acrylicoligomer can comprise acrylate oligomers, methacrylate oligomers,acrylamide oligomers, methacrylamide oligomers, or mixtures of theforegoing. The acrylic oligomers can be monofunctional oligomers (i.e.,oligomers having one acrylate, methacrylate, acrylamide, ormethacrylamide group). The acrylic oligomers also can be difunctionaloligomers (i.e., oligomers having two acrylate, methacrylate,acrylamide, or methacrylamide groups), trifunctional oligomers (i.e.,oligomers having three acrylate, methacrylate, acrylamide, ormethacrylamide groups), tetrafunctional oligomers (i.e., oligomershaving four acrylate, methacrylate, acrylamide, or methacrylamidegroups), pentafunctional oligomers (i.e., oligomers having fiveacrylate, methacrylate, acrylamide, or methacrylamide groups), orhexafunctional oligomers (i.e., oligomers having six acrylate,methacrylate, acrylamide, or methacrylamide groups). Acrylic oligomershaving more than one functional group can comprise the same functionalgroups or different functional groups. A trifunctional acrylic oligomer,for example, can comprise two acrylate groups and one acrylamide group.A trifunctional acrylic oligomer also can comprise, for example, threeacrylate groups. Acrylic oligomers having more than six functionalgroups (e.g., eight or ten functional groups) and mixtures of theforegoing acrylic oligomers also can be used.

Suitable hydrophilic acrylic oligomers include, but are not limited to:polyepoxy acrylates, polyurethane acrylates, polyester acrylates,polyether acrylates, amine-modified polyether acrylates, polyacrylicacrylates, polycarbonate acrylates, polyepoxy methacrylates,polyurethane methacrylates, polyester methacrylates, polyethermethacrylates, amine-modified polyether methacrylates, polyacrylicmethacrylates, polycarbonate methacrylates, polyepoxy acrylamides,polyurethane acrylamides, polyester acrylamides, polyether acrylamides,amine-modified polyether acrylamides, polyacrylic acrylamides,polycarbonate acrylamides, polyepoxy methacrylamides, polyurethanemethacrylamides, polyester methacrylamides, polyether methacrylamides,amine-modified polyether methacrylamides, polyacrylic methacrylamides,polycarbonate methacrylamides, and mixtures of the foregoing. Asdiscussed above, the foregoing acrylic oligomers include one or morefunctional groups, for example, one to six functional groups.

Suitable polyepoxy acrylate oligomers include, but are not limited to:aromatic difunctional epoxy acrylates, acrylated oil epoxy acrylates,phenol formaldehyde epoxy acrylates (also known as novolac epoxyacrylates), aliphatic epoxy acrylates, and mixtures of the foregoing.

Exemplary hydrophilic acrylic oligomers include, but are not limited to:ethoxylated bisphenol A diacrylates (e.g., 30 mole ethoxylated bisphenolA diacrylate), ethoxylated bisphenol A dimethacrylates (e.g., 10 moleethoxylated bisphenol A dimethacrylate), polyethylene glycoldiacrylates, polyethylene glycol dimethacrylates, methoxy polyethyleneglycol acrylates, methoxy polyethylene glycol methacrylates,polypropylene glycol diacrylates, polypropylene glycol dimethacrylates,methoxy polypropylene glycol acrylates, methoxy polypropylene glycolmethacrylates, and mixtures of the foregoing. Ethoxylated acrylates andmethacrylates typically include about 4 to about 100 ethoxy groups, forexample, about 6 to about 70, about 8 to about 50, about 10 to about 40,and/or about 12 to about 30 ethoxy groups. Oligomers containingpolyethylene glycol or polypropylene glycol typically have molecularweights of about 100 g/mol to about 2000 g/mol, for example, about 150g/mol to about 1000 g/mol, about 200 g/mol to about 800 g/mol, and/orabout 300 g/mol to about 600 g/mol.

Multifunctional Acrylic Monomers

Antimicrobial resin compositions in accordance with the presentdisclosure are prepared from a mixture comprising about 10 weight % toabout 80 weight % of a multifunctional acrylic monomer. Suitable rangesinclude, but are not limited to, about 20 weight % to about 60 weight %,and/or about 30 weight % to about 50 weight %. The mixture can comprise,for example, about 10 weight % to about 20 weight %, about 20 weight %to about 30 weight %, about 30 weight % to about 40 weight %, about 40weight % to about 50 weight %, about 50 weight % to about 60 weight %,about 60 weight % to about 70 weight %, and/or about 70 weight % toabout 80 weight % of the multifunctional acrylic monomer. Mixturesincluding more than one acrylic monomer also can be used.

In accordance with the present disclosure, the multifunctional acrylicmonomer can comprise acrylate esters, methacrylate esters, acrylamides,methacrylamides, or mixtures of the foregoing. The multifunctionalacrylic monomers can be difunctional monomers (i.e., monomers having twoacrylate, methacrylate, acrylamide, and/or methacrylamide groups). Themultifunctional acrylic monomers also can be trifunctional monomers,tetrafunctional monomers, pentafunctional monomers, hexafunctionalmonomers, or mixtures of the foregoing. Multifunctional acrylic monomerscan comprise the same functional groups or different functional groups.A difunctional acrylic monomer, for example, can comprise one acrylategroup and one methacrylamide group. A difunctional acrylic monomer alsocan comprise, for example, two methacrylate groups. Multifunctionalacrylic monomers having more than six functional groups (e.g., eight orten functional groups) and mixtures of the foregoing acrylic monomersalso can be used. When exposed to suitable conditions (e.g., a radiationsource, optionally in the presence of an initiator), the alkenylfunctional groups of the multifunctional acrylic monomers can undergointermolecular reactions to form, for example, crosslinked structures.

Suitable multifunctional acrylic monomers include, but are not limitedto: alkoxylated acrylates; alkoxylated methacrylates; linear, branched,or cyclic alkyl acrylates; linear, branched, or cyclic alkylmethacrylates; linear, branched, or cyclic alkyl acrylamides; linear,branched, or cyclic alkyl methacrylamides; linear, branched, or cyclicalkenyl acrylates; linear, branched, or cyclic alkenyl methacrylates;linear, branched, or cyclic alkenyl acrylamides; linear, branched, orcyclic alkenyl methacrylamides; alkoxylated linear, branched, or cyclicalkyl acrylates; alkoxylated linear, branched, or cyclic alkylmethacrylates; alkoxylated linear, branched, or cyclic alkenylacrylates; alkoxylated linear, branched, or cyclic alkenylmethacrylates; heterocyclic acrylates; heterocyclic methacrylates;heterocyclic acrylamides; heterocyclic methacrylamides; and mixtures ofthe foregoing. Difunctional, trifunctional, tetrafunctional,pentafunctional, and hexafunctional derivatives of the foregoing areincluded.

Alkoxylated multifunctional acrylate monomers typically include about 1to about 20 alkoxy groups, for example, about 2 to about 10, about 3 toabout 8, and/or about 4 to about 6 alkoxy groups. Alkoxy groups include,but are not limited to: methoxy groups, ethoxy groups, and propoxygroups.

Alkyl and alkenyl multifunctional acrylic monomers typically compriseabout 4 to about 40 carbon atoms, for example, about 5 to about 21,about 6 to about 18, and/or about 7 to about 15 carbon atoms. The alkyland alkenyl multifunctional acrylic monomers also can comprise more than40 carbon atoms. Heterocyclic multifunctional acrylic monomers typicallycomprise about 5 to about 40 carbon atoms, and one or more heteroatomssuch as N, O, or S.

Exemplary multifunctional acrylic monomers include, but are not limitedto: 1,12-dodecanediol diacrylate, 1,12-dodecanediol dimethacrylate,1,3-butylene glycol diacrylate, 1,3-butylene glycol dimethacrylate,1,4-butanediol diacrylate, 1,4-butanediol dimethacrylate, 1,6-hexanedioldiacrylate, 1,6-hexanediol dimethacrylate, alkoxylated cyclohexanedimethanol diacrylates, alkoxylated cyclohexane dimethanoldimethacrylates, alkoxylated hexanediol diacrylates, alkoxylatedhexanediol dimethacrylates, alkoxylated neopentyl glycol diacrylates,alkoxylated neopentyl glycol dimethacrylates, cyclohexane dimethanoldiacrylate, cyclohexane dimethanol dimethacrylate, diethylene glycoldiacrylate, diethylene glycol dimethacrylate, dipropylene glycoldiacrylate, dipropylene glycol dimethacrylate, ethoxylated bisphenol Adiacrylates, ethoxylated bisphenol A dimethacrylates, ethylene glycoldiacrylate, ethylene glycol dimethacrylate, neopentyl glycol diacrylate,neopentyl glycol dimethacrylate, polyethylene glycol diacrylates,polyethylene glycol dimethacrylates, propylene glycol diacrylates,propylene glycol dimethacrylates, propoxylated neopentyl glycoldiacrylates, propoxylated neopentyl glycol dimethacrylates,tetraethylene glycol diacrylate, tetraethylene glycol dimethacrylate,triethylene glycol diacrylate, triethylene glycol dimethacrylate,tripropylene glycol diacrylate, tripropylene glycol dimethacrylate,ethoxylated trimethylolpropane triacrylates, ethoxylatedtrimethylolpropane trimethacrylates, propoxylated glyceryl triacrylates,propoxylated glyceryl trimethacrylates, trimethylolpropane triacrylate,trimethylolpropane trimethacrylate, pentaerythritol triacrylate,pentaerythritol trimethacrylate, propoxylated trimethylolpropanetriacrylates, propoxylated trimethylolpropane trimethacrylates,tris(2-hydroxyethyl) isocyanurate triacrylate, tris(2-hydroxyethyl)isocyanurate trimethacrylate, di-trimethylolpropane tetraacrylate,dipentaerythritol pentaacrylate, ethoxylated pentaerythritoltetraacrylates, dipentaerythritol pentaacrylate, pentaerythritoltetraacrylate, and mixtures of the foregoing.

Preferred multifunctional acrylic monomers include 1,3-butylene glycoldiacrylate, 1,4-butanediol diacrylate, 1,6-hexanediol diacrylate, andmixtures of the foregoing.

In some embodiments, the multifunctional acrylic monomer and theadhesion-promoting acrylic monomer can be the same.

Adhesion-Promoting Acrylic or Vinyl Monomers

Antimicrobial resin compositions in accordance with the presentdisclosure are prepared from a mixture comprising about 5 weight % toabout 40 weight % of an adhesion-promoting acrylic monomer. Suitableranges include, but are not limited to, about 10 weight % to about 35weight %, and/or about 15 weight % to about 30 weight %. The mixture cancomprise, for example, about 5 weight % to about 10 weight %, about 10weight % to about 15 weight %, about 15 weight % to about 20 weight %,about 20 weight % to about 25 weight %, about 25 weight % to about 30weight %, about 30 weight % to about 35 weight %, and/or about 35 weight% to about 40 weight % of the adhesion-promoting acrylic monomer.Mixtures including more than one adhesion-promoting acrylic monomer alsocan be used.

In accordance with the present disclosure, the adhesion-promotingacrylic monomer can comprise acrylate esters, methacrylate esters,acrylamides, methacrylamides, or mixtures of the foregoing. Theadhesion-promoting acrylic monomers can be monofunctional monomers(i.e., monomers having one acrylate, methacrylate, acrylamide, ormethacrylamide group). The adhesion-promoting acrylic monomers also canbe difunctional monomers, trifunctional monomers, tetrafunctionalmonomers, pentafunctional monomers, hexafunctional monomers, or mixturesof the foregoing. Adhesion-promoting acrylic monomers having more thanone functional group can comprise the same functional groups ordifferent functional groups. A difunctional adhesion-promoting acrylicmonomer, for example, can comprise one acrylate group and onemethacrylamide group. A difunctional adhesion-promoting acrylic monomeralso can comprise, for example, two methacrylate groups.Adhesion-promoting acrylic monomers having more than six functionalgroups (e.g., eight or ten functional groups) and mixtures of theforegoing adhesion-promoting acrylic monomer s also can be used.

In some embodiments, the adhesion-promoting acrylic monomer can be thesame as the multifunctional acrylic monomer.

Adhesion-promoting acrylic or vinyl monomers can be hydrophilic orhydrophobic. Hydrophilic monomers can advantageously provide increasedhydrophilicity to the resin composition. Suitable hydrophilic monomerscan comprise, for example, pendent hydrophilic groups such as alcohols,amines, thiols, carboxylates, phosphates, and sulfates. Exemplaryhydrophilic monomers include, but are not limited to, 1,3-butyleneglycol diacrylate, 1,3-butylene glycol dimethacrylate, 1,4-butanedioldiacrylate, 1,4-butanediol dimethacrylate, 1,6-hexanediol diacrylate,1,6-hexanediol dimethacrylate, 2-hydroxyethyl acrylate, 2-hydroxyethylmethacrylate, 4-hydroxybutyl acrylate, 4-hydroxybutyl methacrylate, and2-(2-ethoxyethoxy)ethyl acrylate.

Suitable adhesion-promoting acrylic monomers include, but are notlimited to: alkoxylated acrylates; alkoxylated methacrylates; linear,branched, or cyclic alkyl acrylates; linear, branched, or cyclic alkylmethacrylates; linear, branched, or cyclic alkyl acrylamides; linear,branched, or cyclic alkyl methacrylamides; linear, branched, or cyclicalkenyl acrylates; linear, branched, or cyclic alkenyl methacrylates;linear, branched, or cyclic alkenyl acrylamides; linear, branched, orcyclic alkenyl methacrylamides; alkoxylated linear, branched, or cyclicalkyl acrylates; alkoxylated linear, branched, or cyclic alkylmethacrylates; alkoxylated linear, branched, or cyclic alkenylacrylates; alkoxylated linear, branched, or cyclic alkenylmethacrylates; heterocyclic acrylates; heterocyclic methacrylates;heterocyclic acrylamides; heterocyclic methacrylamides; caprolactoneacrylates; caprolactone methacrylates; caprolactam acrylamides;caprolactam methacrylamides; valerolactone acrylates; valerolactonemethacrylates; valerolactam acrylamides; valerolactam methacrylamides;butyrolactone acrylates; butyrolactone methacrylates; butyrolactamacrylamides; butyrolactam methacrylamides; propiolactone acrylates;propiolactone methacrylates; propiolactam acrylamides; propiolactammethacrylamides; acrylic acid; and mixtures of the foregoing.Monofunctional, difunctional, trifunctional, tetrafunctional,pentafunctional, and hexafunctional derivatives of the foregoing alsoare included.

Alkoxylated adhesion-promoting acrylic monomers typically include about1 to about 20 alkoxy groups, for example, about 2 to about 10, about 3to about 8, and/or about 4 to about 6 alkoxy groups. Alkoxy groupsinclude, but are not limited to: methoxy groups, ethoxy groups, andpropoxy groups.

Alkyl and alkenyl adhesion-promoting acrylic monomers typically compriseabout 4 to about 40 carbon atoms, for example, about 5 to about 21,about 6 to about 18, and/or about 7 to about 15 carbon atoms. The alkyland alkenyl adhesion-promoting acrylic monomers also can comprise morethan 40 carbon atoms. Heterocyclic adhesion-promoting acrylic monomerstypically comprise about 5 to about 40 carbon atoms, and one or moreheteroatoms such as N, O, or S.

Caprolactone, valerolactone, butyrolactone, and propiolactone acrylatemonomers typically comprise about 1 to about 10 caprolactone,valerolactone, butyrolactone, or propiolactone groups, for example,about 2 to about 8 and/or about 3 to about 6 groups. Caprolactam,valerolactam, butyrolactam, and propiolactam acrylamide monomerstypically comprise about 1 to about 10 caprolactam, valerolactam,butyrolactam, or propiolactam groups, for example, about 2 to about 8and/or about 3 to about 6 groups.

Exemplary adhesion-promoting acrylic monomers include, but are notlimited to: acrylic acid, methacrylic acid, 2-(2-ethoxyethoxy)ethylacrylate, 2-(2-ethoxyethoxy)ethyl methacrylate, 2-phenoxyethyl acrylate,2-phenoxyethyl methacrylate, 3,3,5-trimethylcyclohexyl acrylate,3,3,5-trimethylcyclohexyl methacrylate, alkoxylated lauryl acrylates,alkoxylated lauryl methacrylates, alkoxylated phenol acrylates,alkoxylated phenol methacrylates, alkoxylated tetrahydrofurfurylacrylates, alkoxylated tetrahydrofurfuryl methacrylates, laurylacrylate, lauryl methacrylate, cyclic trimethylolpropane formalacrylate, cyclic trimethylolpropane formal methacrylate,dicyclopentadienyl acrylate, dicyclopentadienyl methacrylate, diethyleneglycol methyl ether acrylate, diethylene glycol methyl ethermethacrylate, ethoxylated hydroxyethyl acrylates, ethoxylatedhydroxyethyl methacrylates, ethoxylated nonyl phenol acrylates,ethoxylated nonyl phenol methacrylates, isobornyl acrylate, isobornylmethacrylate, isodecyl acrylate, isodecyl methacrylate, isoocylacrylate, isoocyl methacrylate, metallic acrylates, metallicmethacrylates, methoxy polyethylene glycol acrylates, methoxypolyethylene glycol methacrylates, octyldecyl acrylate, octyldecylmethacrylate, polypropylene glycol acrylates, polypropylene glycolmethacrylates, propoxylated allyl acrylates, propoxylated allylmethacrylates, stearyl acrylate, stearyl methacrylate,tetrahydrofurfuryl acrylate, tetrahydrofurfuryl methacrylate, tridecylacrylate, tridecyl methacrylate, triethylene glycol ethyl etheracrylate, triethylene glycol ethyl ether methacrylate, 1,12-dodecanedioldiacrylate, 1,12-dodecanediol dimethacrylate, 1,3-butylene glycoldiacrylate, 1,3-butylene glycol dimethacrylate, 1,4-butanedioldiacrylate, 1,4-butanediol dimethacrylate, 1,6-hexanediol diacrylate,1,6-hexanediol dimethacrylate, alkoxylated cyclohexane dimethanoldiacrylates, alkoxylated cyclohexane dimethanol dimethacrylates,alkoxylated hexanediol diacrylates, alkoxylated hexanedioldimethacrylates, alkoxylated neopentyl glycol diacrylates, alkoxylatedneopentyl glycol dimethacrylates, cyclohexane dimethanol diacrylate,cyclohexane dimethanol dimethacrylate, diethylene glycol diacrylate,diethylene glycol dimethacrylate, dipropylene glycol diacrylate,dipropylene glycol dimethacrylate, ethoxylated bisphenol A diacrylates,ethoxylated bisphenol A dimethacrylates, ethylene glycol diacrylate,ethylene glycol dimethacrylate, neopentyl glycol diacrylate, neopentylglycol dimethacrylate, polyethylene glycol diacrylates, polyethyleneglycol dimethacrylates, propylene glycol diacrylates, propylene glycoldimethacrylates, propoxylated neopentyl glycol diacrylates, propoxylatedneopentyl glycol dimethacrylates, tetraethylene glycol diacrylate,tetraethylene glycol dimethacrylate, triethylene glycol diacrylate,triethylene glycol dimethacrylate, tripropylene glycol diacrylate,tripropylene glycol dimethacrylate, ethoxylated trimethylolpropanetriacrylates, ethoxylated trimethylolpropane trimethacrylates,propoxylated glyceryl triacrylates, propoxylated glyceryltrimethacrylates, trimethylolpropane triacrylate, trimethylolpropanetrimethacrylate, pentaerythritol triacrylate, pentaerythritoltrimethacrylate, propoxylated trimethylolpropane triacrylates,propoxylated trimethylolpropane trimethacrylates, tris(2-hydroxyethyl)isocyanurate triacrylate, tris(2-hydroxyethyl) isocyanuratetrimethacrylate, di-trimethylolpropane tetraacrylate, dipentaerythritolpentaacrylate, ethoxylated pentaerythritol tetraacrylates,dipentaerythritol pentaacrylate, pentaerythritol tetraacrylate, andmixtures of the foregoing.

Exemplary adhesion-promoting acrylic monomers also include, but are notlimited to: 3,3,5-trimethylcyclohexyl acrylamide,3,3,5-trimethylcyclohexyl methacrylamide, dicyclopentadienyl acrylamide,dicyclopentadienyl methacrylamide, isobornyl acrylamide, isobornylmethacrylamide, isodecyl acrylamide, isodecyl methacrylamide, isoocylacrylamide, isoocyl methacrylamide, octyldecyl acrylamide, octyldecylmethacrylamide, stearyl acrylamide, stearyl methacrylamide,tetrahydrofurfuryl acrylamide, tetrahydrofurfuryl methacrylamide,tridecyl acrylamide, tridecyl methacrylamide, dimethyl acrylamide,dimethyl methacrylamide, and mixtures of the foregoing.

Preferred adhesion-promoting acrylic monomers include acrylic acid,N,N-dimethyl acrylamide, 1,3-butylene glycol diacrylate, 1,4-butanedioldiacrylate, 1,6-hexanediol diacrylate, 2-hydroxyethyl methacrylate,4-hydroxybutyl acrylate, tetrahydrofurfuryl acrylate,2-(2-ethoxyethoxy)ethyl acrylate, and mixtures of the foregoing.

Adhesion-promoting vinyl monomers include, for example, N-vinylpyrrolidone.

Antimicrobial Metal Salts

Antimicrobial resin compositions in accordance with the presentdisclosure are prepared from a mixture comprising about 0.1 weight % toabout 15 weight % of an antimicrobial metal salt. Suitable rangesinclude, but are not limited to, about 0.5 weight % to about 10 weight%, and/or about 1 weight % to about 8 weight %. The mixture cancomprise, for example, about 0.1 weight % to about 1 weight %, about 1weight % to about 5 weight %, about 5 weight % to about 10 weight %,and/or about 10 weight % to about 15 weight % of the metal salt.Mixtures including more than one metal salt also can be used.

In accordance with the present disclosure, the antimicrobial metal saltcan comprise metal salts including, but not limited to, salts of silver,copper, gold, zinc, cerium, platinum, palladium, tin, and mixtures ofthe foregoing. Mixtures of metals salts also can be used. Suitable metalsalts include, but are not limited to metal sulfadiazines, metal halides(e.g., metal fluorides, metal chlorides, metal bromides, metal iodides),metal acetates, metal hydroxides, metal carbonates, metal oxalates,metal phosphates, metal sulfates, metal chlorates, metal bromates, metaliodates, and mixtures of the foregoing. Exemplary metal salts include,but are not limited to, silver salts, such as silver sulfadiazine,silver halides (e.g., silver fluoride, silver chloride, silver bromide,silver iodide), silver acetate, silver hydroxide, silver carbonate,silver oxalate, silver phosphate, silver sulfate, silver chlorate,silver bromate, silver iodate, and mixtures of the foregoing.

The metal salt in accordance with the present disclosure can compriseparticles, such as microparticles or nanoparticles. The metal saltparticles typically have a diameter in the range of about 1 nanometer toabout 50 micrometers, for example, from about 10 nanometers to about 25micrometers, from about 50 nanometers to about 10 micrometers, and/orfrom about 100 nm to about 1 micrometer.

Initiators

Antimicrobial resin compositions in accordance with the presentdisclosure optionally can be prepared from a mixture comprising about0.1 weight % to about 15 weight % of an initiator. Suitable rangesinclude, but are not limited to, about 0.5 weight % to about 10 weight%, and/or about 1 weight % to about 8 weight %. The mixture cancomprise, for example, about 0.1 weight % to about 1 weight %, about 1weight % to about 5 weight %, about 5 weight % to about 10 weight %,and/or about 10 weight % to about 15 weight % of the initiator. Mixturesincluding more than initiator also can be used.

Suitable initiators include, but are not limited to: α-hydroxyketones,phenylglyoxylates, benzyldimethyl ketals, α-aminoketones, mono acylphosphines, bis acyl phosphines, phosphine oxides, metallocenes (e.g.,fluorinated diaryl titanocenes such as IRGACURE® 784), iodonium salts,mercaptobenzothiazoles, mercptobenzooxazoles, benzophenones,acetophenones, benzoin alkyl ethers, hexaarylbisimidazoles, and mixturesthereof.

Exemplary photoinitiators include, but are not limited to:1-hydroxycyclohexyl phenyl ketone, benzophenone,2-hydroxy-2-methyl-1-phenyl-1-propanone,2-hydroxy-1-[4-(2-hydroxyethoxy)phenyl]-2-methyl-1-propanone,methylbenzoylformate, oxy-phenyl-acetic acid2-[2-oxo-2-phenyl-acetoxy-ethoxy]-ethyl ester, oxy-phenyl-acetic acid2-[2-hydroxy-ethoxy]-ethyl ester, α,α-dimethoxy-α-phenylacetophenone,2-benzyl-2-(dimethylamino)-1-[4-(4-morpholinyl)phenyl]-1-butanone,2-methyl-1-[4-(methylthio)phenyl]-2-(4-morpholinyl)-1-propanone,diphenyl (2,4,6-trimethylbenzoyl)-phosphine oxide, phenylbis(2,4,6-trimethyl benzoyl) phosphine oxide,bis(η⁵-2,4-cyclopentadien-1-yl)bis[2,6-difluoro-3-(1H-pyrrol-1-yl)phenyl]titanium,(4-methylphenyl)-[4-(2-methylpropyl)phenyl]-iodoniumhexafluorophosphate, 2,2-dimethoxy-1,2-diphenylethan-1-one,2,4,6-trimethylbenzoyldiphenylphosphine oxide (LUCIRIN TPO®), andmixtures of the foregoing.

Additional suitable initiators include, but are not limited to:azobisbutyronitrile and dibenzoyl peroxides.

Additives

The antimicrobial resin formulations optionally comprise one or moreadditives. Suitable additives include, but are not limited to:photoinitiators (e.g., benzophenone and pyruvic acid), stabilizers,chain transfer agents, plasticizers, light stabilizers, UV screeningcompounds, leveling agents, wetting agents, preservatives, adhesionpromoters, emulsifiers, pigments, dyes (e.g., eosin, methylene blue, andketocumarines), or fillers. The optional additives typically compriseabout 0.1 weight % to about 20 weight % of the formulations, forexample, about 0.5 weight % to about 15 weight %, about 1 weight % toabout 10 weight %, and/or about 2 weight % to about 5 weight %.

The additive can comprise saturated fatty acids, unsaturated fattyacids, or mixtures thereof. Fatty acids can advantageously stabilizesilver salt dispersions, thereby maintaining the silver salt in a highlydispersed state during the curing step. Suitable fatty acids include,but are not limited to: decanoic acid, lauric acid, myristic acid,palmitic acid, stearic acid, eicosanoic acid, docsanoic acid,tetracosanoic acid, α-linolenic acid, stearidonic acid, eicosapentaenoicacid, docosahexaenoic acid, linoleic acid, γ-linolenic acid,dihomo-γ-linolenic acid, arachidonic acid, oleic acid, erucic acid,nervonic acid, or mixtures of the foregoing. Quaternary ammoniumcompounds also can provide stabilization of silver salt dispersions.

Suitable fillers for the formulations according to the disclosureinclude, for example, polymers soluble in the reactive acrylic monomers,such as polyvinyl alcohol and polyvinyl butyrate.

Antimicrobial Resins

The antimicrobial resins of the present disclosure are formed byproviding a mixture comprising one or more hydrophilic acrylicoligomers, one or more multifunctional acrylic monomers, one or moreadhesion-promoting acrylic or vinyl monomers, and one or moreantimicrobial metal salts; and exposing the mixture to a radiationsource. Exposure of the mixture to the radiation source cures at least aportion of the mixture. Combining the aforementioned components andexposing same to radiation provides more efficacious antimicrobialresins, as previously discussed. Additionally, the components have beenselected so that the formed resin is hydrophilic and has hydrogel-likeproperties such that it is compatible with biological tissues.Hydrophilicity advantageously can promote continuous and rapid releaseof the antimicrobial metal salt from the resin into aqueous solution.Furthermore, the antimicrobial resins of the present disclosure comprisecomponents that advantageously promote the stabilization of metal saltdispersions, thereby facilitating the preparation of more homogeneouslydispersed resins comprising difficult to disperse metal salts (e.g.,silver sulfadiazine). As previously discussed, more homogeneouslydispersed metal salts can have improved efficacy and/or more desirableelution profiles.

The radiation source can comprise an ultraviolet (UV) light source, anelectron beam source, a gamma radiation source, a X-ray source, an ionbeam source, a microwave source, a heat source, or a combination of theforegoing. Generally where electron beam radiation is used, the amountcan be from about 1 to about 10 Mrads, for example, from about 3 toabout 8 Mrads. Where a UV light source is used, the radiation amount canbe from about 0.1 J/cm² to about 5 J/cm².

In accordance with the methods of the present disclosure, theantimicrobial resins can be formed on a substrate surface by providing amixture comprising one or more hydrophilic acrylic oligomers, one ormore multifunctional acrylic monomers, one or more adhesion-promotingacrylic or vinyl monomers, and one or more metal salts, providing themixture on the substrate surface, and exposing the mixture to aradiation source. The mixture can be provided on the substrate surfaceby various manual and mechanical means of application, for example, byspreading, layering, dipping, coating, swabbing, spraying, pouring,and/or washing. Prior to providing the mixture on the substrate surface,the mixture typically has a viscosity of about 50 centipoise (cP) toabout 1000 cP, for example, about 100 cP to about 800 cP, about 200 cPto about 600 cP, and/or about 300 cP to about 500 cP, but higher andlower viscosities also can be used.

The antimicrobial resins in accordance with the present disclosurecomprise about 15 weight % to about 80 weight % of hydrophilic acrylicoligomer units, about 10 weight % to about 80 weight % ofmultifunctional acrylic monomer units, about 5 weight % to about 40weight % of adhesion-promoting acrylic or vinyl monomer units, and about0.1 weight % to about 15 weight % of an antimicrobial metal salt. Thehydrophilic acrylic oligomer units, the multifunctional acrylic monomerunits, and the adhesion-promoting acrylic or vinyl monomer units of theantimicrobial resins are typically substantially cured, or cross-linked,after exposure to radiation.

The present disclosure also is directed to an antimicrobial resincomposition prepared by a process comprising: providing a mixturecomprising about 15 weight % to about 80 weight % of a hydrophilicacrylic oligomer, about 10 weight % to about 80 weight % of amultifunctional acrylic monomer, about 5 weight % to about 40 weight %of an adhesion-promoting acrylic or vinyl monomer, and about 0.1 weight% to about 15 weight % of an antimicrobial metal salt; and exposing themixture to a radiation source to cure at least a portion of the mixture,thereby forming an antimicrobial resin.

The disclosure may be better understood by reference to the followingexamples which are not intended to be limiting, but rather only setforth exemplary embodiments in accordance with the disclosure.

EXAMPLES Example 1 Preparation of Antimicrobial Resins on PolycarbonateSurfaces

An antimicrobial resin was prepared by combining SR 610 polyethyleneglycol diacrylate (23.63 weight %), CD9038 ethoxylated bisphenol Adiacrylate (28.35 weight %), acrylic acid (9.45 weight %), dimethylacrylamide (9.45 weight %), SR 238 hexanediol diacrylate (9.45 weight%), 2-hydroxyethyl methacrylate (9.45 weight %), stearic acid (0.50weight %), and silver sulfadiazine (5.00 weight %). IRGACURE® 651α,α-dimethoxy-α-phenylacetophenone initiator (4.72 weight %) was added,and the resulting mixture was applied to a polycarbonate surface. Thepolycarbonate surface was then exposed to a UV light source(approximately 0.5 J/cm²) to cure the mixture, thereby forming a coatingcomprising an antimicrobial resin on the polycarbonate surface. Thecured antimicrobial resin adhered strongly to the polycarbonate surface.

Component Weight % Function Supplier IRGACURE ® 651 (α,α- 4.72 InitiatorCiba dimethoxy-α- phenylacetophenone) SR 610 (polyethylene 23.63Oligomer/ Sartomer glycol-600 diacrylate) monomer CD 9038 (30 moleethoxylated 28.35 Oligomer Sartomer bisphenol A diacrylate) Acrylic acid9.45 Monomer Aldrich Dimethyl acrylamide 9.45 Monomer Aldrich SR 238(1,6-hexanediol 9.45 Monomer Sartomer diacrylate) 2-Hydroxyethylmethacrylate 9.45 Monomer Aldrich Silver sulfadiazine 5.00 AntimicrobialAldrich agent Stearic acid 0.50 Emulsifier Aldrich

The antimicrobial resin formed after UV curing was observed to behydrophilic, and rapidly increased in weight due to the absorption ofwater (data not shown). Hydrophilicity advantageously can promotecontinuous and rapid release of the antimicrobial metal salt from theresin into aqueous solution.

The elution profile of silver ions released from the antimicrobial resinwas tested by placing the polycarbonate surface carrying theantimicrobial resin in aqueous solution and detecting silver ion levels.An initial burst of silver ions was released within approximately 30minutes of the start of the measurements. After the initial burst, therelease of silver ions declined slightly, stabilizing at about 50minutes after the start of the experiment (see FIG. 1, Sample B) andproviding sustained release of a relatively high concentration of silverfor at least 48 hours. High total amounts of silver ion were releasedover 96 hours by the antimicrobial resin prepared in accordance with thedisclosed methods (see FIG. 2, Sample B). In contrast, coatings ofapproximately the same thicknesses prepared from formulations not inaccordance with the disclosure released lower overall levels of silver(see FIG. 2, Samples C and D), and did not exhibit sustained release ofa relatively high concentration of silver ions (see FIG. 1, Samples A,C, and D). The coating of comparative Sample A included asilver-containing polyvinyl alcohol hydrogel layer prepared inaccordance with the disclosure of U.S. Patent Publication No.2008/0063693. The coating of comparative Sample C included silvernanoparticles and a stabilizing agent and was prepared in accordancewith the disclosure of U.S. Patent Publication No. 2007/0003603. Thecoating of comparative Sample D was prepared by blending 8% ALPHA-SAN®antimicrobial silver additive (available from Milliken & Company,Spartanburg, S.C.) in MAKROLON® Rx-1805 medical grade polycarbonateresin (available from Bayer MaterialsScience, Pittsburgh, Pa.) andapplying the coating to a substrate surface.

Example 2 Antimicrobial Activity of Radiation-Cured Resins

The antimicrobial resin-carrying polycarbonate surface prepared inExample 1 was tested to determine its ability to inhibit growth ofmicroorganisms. Polycarbonate surfaces carrying coatings comprisingantimicrobial resins not in accordance with the disclosure (seeExample 1) and an uncoated polycarbonate surface were also tested. Asuspension of Staphylococcus aureus (S. aureus) was grown in tryptic soybroth for 18-24 hours. The suspension was then diluted in saline to6.4×10⁵ colony-forming units per mL (cfu/mL). Tubes containing 5 mLsaline were inoculated with 0.1 mL (6.4×10⁴ cfu) of the suspension.Samples A-D and an uncoated polycarbonate surface were aseptically addedto the tubes, which were incubated at 20-25° C. for 48 hours. Thesamples then were plated in tryptic soy agar in triplicate and incubatedat 30-35° C. for 48 hours. After this time, growth of S. aureus wasmeasured, as shown in FIG. 3. The antimicrobial resin prepared inaccordance with the disclosure (see FIG. 3, Sample B) displayed about10-fold improved antimicrobial activity 96 hours after treatment with S.aureus, compared to the antimicrobial resins not prepared in accordancewith the disclosed methods (see FIG. 3, Samples A, C and D) and theuncoated polycarbonate surface (see FIG. 3, Control).

What is claimed is:
 1. An antimicrobial resin composition comprising:about 15 weight % to about 80 weight % of hydrophilic acrylic oligomerunits; about 10 weight % to about 80 weight % of multifunctional acrylicmonomer units; about 5 weight % to about 40 weight % of monofunctionaladhesion-promoting acrylic or vinyl monomer units; and about 0.1 weight% to about 15 weight % of an antimicrobial metal salt; wherein thehydrophilic acrylic oligomer units, the multifunctional acrylic monomerunits, and the monofunctional adhesion-promoting acrylic or vinylmonomer units are substantially cured.
 2. An antimicrobial resincomposition prepared by the process comprising: providing a mixturecomprising about 15 weight % to about 80 weight % of a hydrophilicacrylic oligomer, about 10 weight % to about 80 weight % of amultifunctional acrylic monomer, about 5 weight % to about 40 weight %of a monofunctional adhesion-promoting acrylic or vinyl monomer, andabout 0.1 weight % to about 15 weight % of an antimicrobial metal salt;and exposing the mixture to a radiation source to cure at least aportion of the mixture, thereby forming an antimicrobial resin.
 3. Thecomposition of claim 1, wherein the hydrophilic acrylic oligomer unitscomprise monofunctional oligomers, difunctional oligomers, trifunctionaloligomers, tetrafunctional oligomers, pentafunctional oligomers,hexafunctional oligomers, or mixtures thereof.
 4. The composition ofclaim 1, wherein the hydrophilic acrylic oligomer units comprisepolyepoxy acrylates, polyurethane acrylates, polyester acrylates,polyether acrylates, amine-modified polyether acrylates, polyacrylicacrylates, polycarbonate acrylates, polyepoxy methacrylates,polyurethane methacrylates, polyester methacrylates, polyethermethacrylates, amine-modified polyether methacrylates, polyacrylicmethacrylates, polycarbonate methacrylates, polyepoxy acrylamides,polyurethane acrylamides, polyester acrylamides, polyether acrylamides,amine-modified polyether acrylamides, polyacrylic acrylamides,polycarbonate acrylamides, polyepoxy methacrylamides, polyurethanemethacrylamides, polyester methacrylamides, polyether methacrylamides,amine-modified polyether methacrylamides, polyacrylic methacrylamides,polycarbonate methacrylamides, or mixtures thereof.
 5. The compositionof claim 1, wherein the hydrophilic acrylic oligomer units compriseethoxylated bisphenol A diacrylates, polyethylene glycol diacrylates, ormixtures thereof.
 6. The composition of claim 1, wherein themultifunctional acrylic monomer units comprise acrylate esters,methacrylate esters, acrylamides, methacrylamides, or mixtures thereof.7. The composition of claim 1, wherein the multifunctional acrylicmonomer units comprise difunctional monomers, trifunctional monomers,tetrafunctional monomers, pentafunctional monomers, hexafunctionalmonomers, or mixtures thereof.
 8. The composition of claim 1, whereinthe multifunctional acrylic monomer units comprise 1,3-butylene glycoldiacrylate, 1,4-butanediol diacrylate, 1,6-hexanediol diacrylate, ormixtures thereof.
 9. The composition of claim 1, wherein themonofunctional adhesion-promoting acrylic or vinyl monomer unitscomprise acrylate esters, methacrylate esters, acrylamides,methacrylamides, or mixtures thereof.
 10. The composition of claim 1,wherein the monofunctional adhesion-promoting acrylic or vinyl monomerunits comprise acrylic acid, N,N-dimethyl acrylamide, 2-hydroxyethylmethacrylate, 4-hydroxybutyl acrylate, tetrahydrofurfuryl acrylate,2-(2-ethoxyethoxy) ethyl acrylate, N-vinyl pyrrolidone, or mixturesthereof.
 11. The composition of claim 1, wherein the metal saltcomprises a metal selected from the group consisting of silver, copper,gold, zinc, cerium, and mixtures thereof.
 12. The composition of claim1, wherein the metal salt comprises silver.
 13. The composition of claim1, wherein the metal salt comprises silver sulfadiazine.
 14. Thecomposition of claim 1, wherein the metal salt comprises particleshaving a diameter of about 1 nanometer to about 50 micrometers.
 15. Thecomposition of claim 1, wherein the metal salt comprises silversulfadiazine particles.
 16. The composition of claim 1, furthercomprising a saturated fatty acid, an unsaturated fatty acid, or amixture thereof.
 17. The composition of claim 1, further comprising afatty acid selected from the group consisting of: decanoic acid, lauricacid, myristic acid, palmitic acid, stearic acid, eicosanoic acid,docsanoic acid, tetracosanoic acid, a-linolenic acid, stearidonic acid,eicosapentaenoic acid, docosahexaenoic acid, linoleic acid, γ-linolenicacid, dihomo-γ-linolenic acid, arachidonic acid, oleic acid, erucicacid, nervonic acid, and mixtures thereof.
 18. The composition of claim1, wherein the hydrophilic acrylic oligomer units are is selected fromthe group consisting of difunctional oligomers, trifunctional oligomers,tetrafunctional oligomers, pentafunctional oligomers, hexafunctionaloligomers, and mixtures thereof, and wherein the multifunctional acrylicmonomer is selected from the group consisting of alkyl multifunctionalmonomers and alkenyl multifunctional monomers.
 19. The composition ofclaim 2, wherein the radiation source comprises an ultraviolet (UV)light source, an electron beam source, a gamma radiation source, anX-ray source, an ion beam source, a microwave source, a heat source, ora combination of the foregoing.
 20. The composition of claim 2, whereinthe mixture further comprises about 0.1 weight % to about 15 weight % ofan initiator.